H ax vs. H eq migrations in tetrahydropyranylidenes generated by Bamford-Stevens reactions. Temperature dependence and non-stereoselective activation by ring oxygen

Abstract

For 1,2-shifts in singlet carbenes, a tetrahydropyranyl oxygen strongly activates its adjacent H's. To determine whether this activation is stereoselective for H ax or H eq, we studied d-labeled analogs of 17a-oxa-D-homosteroidal C- 16 ketones ( 6a). A putative carbene center was generated at C-16 by thermal and photic Bamford-Stevens reactions, and the relative proportions of H and D shift from C-17 were assayed. After correction for primary H/D isotope effects, the H ax/H eq migration ratios in thermolysis were 2.2 at 170°C, 3.3 at 120°C, and 4.1 at 95°C; and in photolysis it was 4.4 at −70°C. The ratio at 170°C is virtually the same as for ordinary cyclohexylidenes under comparable thermal conditions, so the ring oxygen activates H ax and H eq non-stereoselectively. Graphical analysis of the temperature dependence in thermolysis gave ΔE a (or Δ(ΔH ‡)) = 2.7 k cal/mol (in favor of H ax) and Δ(ΔS ‡) 4.5 e.u. (in favor of H eq). Extrapolation indicates the H ax/H eq ratio would be ca. 10 at room temperature, corresponding to Δ(ΔG ‡) = ca. 1.35 kcal/mol.